Inhibitory effect of ethanol extract of Piper longum L. on rabbit platelet aggregation through antagonizing thromboxane A2 receptor

Piper longum L. has been used as a crude drug for the treatment of disorders of poor peripheral blood circulation in Asia. However, the detailed mechanism of its action has not been clarified as yet. In the present study, we examined the effects of several extracts of Piper longum L. on rabbit platelet function. Thromboxane A(2) receptor agonist U46619 caused rabbit platelet aggregation, which was potently inhibited by the ethanol or butanol extract of Piper longum L. The ethanol extract inhibited U46619-induced platelet aggregation in a concentration-dependent manner, but only weakly inhibited that induced by thrombin. The maximum response to U46619 was reduced by 100% ethanol extract concentration dependently, suggesting that the inhibitory mode of U46619-induced platelet aggregation by the ethanol extract was non-competitive. The extract also inhibited U46619-induced phosphoinositide hydrolysis with a similar concentration dependency to the platelet aggregation. Furthermore, the extract inhibited binding of (3)H]SQ29548 to thromboxane A(2) receptor in intact platelets in a concentration-dependent manner. These results suggest that Piper longum L. contains a constituent(s) that inhibits platelet aggregation as a non-competitive thromboxane A(2) receptor antagonist.